天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (4): 267-270.doi: 10.11958/20192502

• 实验研究 • 上一篇    下一篇

1,25-二羟维生素D3通过TGF-β1（/ Smad2/3）影响的ROS调节气道重塑 #br#

张鹤，张沄，王宋平
  

  1. 泸州市西南医科大学附属医院呼吸内一科（邮编 646000）
  • 收稿日期:2019-08-16 修回日期:2020-01-02 出版日期:2020-04-15 发布日期:2020-06-23
  • 作者简介:张鹤（1993），女，硕士研究生在读，主要从事呼吸系统疾病的临床研究
  • 基金资助:
    四川省卫计委课题资助项目（18PJ402）

Effects of 1, 25-dihydroxyvitamin D3 on ROS regulating airway#br# remodeling through TGF-β1/(Smad2/3) #br#

ZHANG He, ZHANG Yun, WANG Song-ping #br#   

  1. Department of Respiration, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China
  • Received:2019-08-16 Revised:2020-01-02 Published:2020-04-15 Online:2020-06-23

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摘要： 目的 探讨 1，25-二羟维生素 D3［1，25-（OH）2D3］通过转化生长因子-β1（TGF-β1）（/ Smad2/3）对活性氧
（ROS）的影响及调节气道重塑的分子机制。方法 选取健康雌性 Balb/c小鼠 24只，随机分为正常组（A组）、哮喘组
（B组）、1，25-（OH）2D3+哮喘组（C组）。B组和 C组于第 0、7、14天腹腔注射 0.5 mL致敏液（10 µg卵清蛋白与 2 mg铝制剂），之后用卵清蛋白雾化吸入，于第 21~27天每天雾化 1次，第 28~77天隔天雾化 1次制备小鼠支气管哮喘气道重
塑模型。C组在每次雾化激发前 30 min予以腹腔注射 100 ng 1，25-（OH）2D3，实验过程持续至少 77 d。收集小鼠肺组
织分别用于 HE染色、AB-PAS染色、Masson染色分析小鼠气道病理形态改变、气道黏液高分泌及气道重塑，运用计算
机图像分析系统评价各组气道重塑情况。用免疫荧光检测气道 ROS的表达，Western blot检测 TGF-β1、Smad2/3的表
达水平。结果 B组较 A组气道受损明显，可见大量炎性细胞浸润，黏液分泌增加，上皮下胶原沉积明显增多，与 B
组相比，C组病理形态损伤表现明显缓解，但仍较 A组加重；B组较 A组 ROS，TGF-β1、Smad2/3蛋白的表达水平明显
升高。与 B组相比，C组 ROS，TGF-β1、Smad2/3蛋白的表达降低，但仍较 A组升高（P＜0.01）。结论 1，25-（OH）2D3
可能通过抑制 TGF-β1（/ Smad2/3）的表达从而减少 ROS水平，达到调节小鼠气道重塑的作用。

关键词: 骨化三醇, 哮喘, 气道重塑, 活性氧, 转化生长因子-β1, 1,25-二羟维生素 D3

Abstract: Objective To explore the effect of 1, 25-dihydroxyvitamin D3［1, 25-(OH)2D3］on reactive oxygen species
(ROS) through transforming growth factor- β1(TGF- β1)/(Smad2/3) and molecular mechanism of regulating airway
remodeling. Methods Twenty-four healthy female Balb/c mice were randomized into control group (group A), asthma group
(group B), and asthma treated with 1, 25-(OH)2D3 group (group C). The group B and group C were sensitized with ovalbumin via intraperitoneal injection at the day 0, 7, and 14, and ovalbumin was also given by aerosol inhalation, once a day from the day 21 to 27, and once every other day from day 28 to 77 to build the airway remodeling model of bronchial asthma of mice.
Group C was given 100 ng of 1, 25-(OH)2D3 via intraperitoneal injection half an hour before each aerosol challenge, and the experimental process lasted at least 77 days. The lung tissues of mice were collected for HE staining, AB-PAS staining, and Masson staining to analyze the airway pathological changes, high secretion of airway mucus, and airway remodeling status. The computer image analysis system was used to evaluate the airway remodeling. Airway ROS expression was tested by immunofluorescence. The expression levels of TGF- β1 and Smad2/3 were tested with Western blot assay. Results Compared with group A, the airways was significantly damaged in group B with large amount of inflammatory cell infiltration, increased mucus secretion and increased subepithelial collagen deposition. Compared with group B, the pathological and morphological damages were significantly relieved in group C, but still more severe than those of group A. The expression levels of ROS, TGF-β1 and Smad2/3 proteins were significantly higher in group B than those in group A. Compared with group B, the expressions of ROS, TGF- β1 and Smad2/3 proteins were reduced in group C, but still higher than those in group A (P＜0.01). Conclusion 1, 25- (OH)2D3 may reduce the ROS level by inhibiting the expressions of TGF- β1/(Smad2/3), and thereby regulating the airway remodeling in mice.

Key words: calcitriol, asthma, airway remodeling, reactive oxygen species(ROS), transforming growth factor-β1(TGF-
β1), 1, 25-dihydroxyvitamin D3

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